Statin Pleiotropy Against Renal Injury

Abstract

Statins may exhibit significant renoprotective effects beyond their lipid-lowering capacity. Herein, the authors review data from human and animal models of renal disease as well as from studies in cultured renal cells with regard to extralipid renoprotective properties of statins. Statins may exert lipid-independent benefits against renal injury in experimental states of chronic or acute renal function impairment. These include diabetic and hypertensive glomerulosclerosis, autoimmune glomerulonephritis, ischemia/reperfusion-induced renal damage, and unilateral ureteral obstructive nephropathy. Also, statins, by reducing the synthesis of mevalonate products, inhibit the activation of Rho and Ras guanosine triphosphatases that may influence various signaling pathways involving renal inflammatory, fibrogenic, proliferative, and cell-death responses. Therefore, statins exert anti-inflammatory actions in renal tissue, prevent renal scarring, and diminish mesangial or other kidney cell–type proliferation while promoting mesangial cell apoptosis. Renal antioxidant effects with consequent endothelial function regulation of renal vasculature following statin treatment may also account for pleiotropic protection against renal injury.